Abstract
Objectives
As the main cause of osteoporosis, abnormal activity of osteoclasts could disrupt the balance between bone resorption and formation. Moreover, up-regulation of nuclear factor-kappa ligand (RANKL) expression by chronic inflammation-mediated inflammatory factors might contribute to the differentiation of osteoclast precursor cells. Therefore, an anti-inflammatory agent named yangonin was presented for inhibiting osteoclast and relieving inflammatory osteoporosis through down-regulating inflammatory factors.
Methods
We established a model of macrophage inflammation and then verified the anti-inflammatory effect of yangonin. The inhibitory effect of yangonin on osteoclasts was detected by tartrate-resistant acid phosphatase (TRAP) staining, Western blotting and quantitative real-time PCR (qRT-PCR). Finally, micro-CT, TRAP and hematoxylin–eosin (HE) staining were used to show the effect of yangonin on inflammatory osteoporosis in vivo.
Results
Our results suggested that yangonin was able to reduce the secretion of inflammatory factors, down-regulate osteoclast-related genes such as TRAP, RANKL, cathepsin K (CTSK) and nuclear factor-activated T-cell 1 (NFATc1). Furthermore, it was demonstrated that yangonin could suppress the function of inflammatory cytokines in osteoclast differentiation and reporting, wherein NF-κB, AKT and downstream c-Fos/NFATc1 signaling pathways were involved. In an in vivo study, we implied that yangonin has a relieving effect on inflammatory osteoporosis.
Conclusion
Our research shows that yangonin down-regulates inflammatory factors and inhibits the bone-breaking effect of inflammation through NF-κB, AKT and downstream c-Fos/NFATc1 signaling pathways to achieve the purpose of treating inflammatory osteoporosis.
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Data availability statement
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation, to any qualified researcher.
Abbreviations
- RANKL:
-
Receptor activator of nuclear factor-kappa ligand
- LPS:
-
Lipopolysaccharide
- CM:
-
Conditional medium
- HE:
-
Hematoxylin–eosin
- TRAP:
-
Tartrate-resistant acid phosphatase
- CTSK:
-
Cathepsin K
- NFATc1:
-
Nuclear factor-activated T-cell 1
- M-CSF:
-
Macrophage colony stimulation factor
- TRAF6:
-
Tumor necrosis factor receptor-associated factor 6
- TNF-α:
-
Tumor necrosis factor-α
- BMDM:
-
Bone marrow-derived macrophages/monocytes
- RIPA:
-
Radio-immunoprecipitation assay buffer
- PMSF:
-
Phenylmethanesulfonyl fluoride
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Funding
This study was supported by the Natural Science Foundation of Zhejiang Province (LY20H060006), Experimental Animal Science Project of Zhejiang Province (LGD19H310001). The authors thank Professor Li Wang of Research Center for Integrated Medicine Affiliated Traditional Medicine Hospital of Southwest Medical University for his guidance.
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HC and FL conceived the study. FL and HH contributed to the acquisition and interpretation of data. FL and XW did the data cleaning, statistical analysis and model building with assistance from ZJ, XS, XJ, LC and JS. FL and HH drafted the manuscript. All authors contributed to the critical revision of the manuscript for important intellectual content. All authors critically reviewed the manuscript for important intellectual content and gave final approval for the version to be published.
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Lu, F., Wu, X., Hu, H. et al. Yangonin treats inflammatory osteoporosis by inhibiting the secretion of inflammatory factors and RANKL expression. Inflammopharmacol 30, 1445–1458 (2022). https://doi.org/10.1007/s10787-022-00985-1
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DOI: https://doi.org/10.1007/s10787-022-00985-1